ABSTRACT Many recent studies have demonstrated the efficacy of interstitial ablative approaches for the treatment of hepatic tumors, including chemical ablation, cryoablation, and thermal ablation using energy sources like RF, laser, microwave, or focused ultrasound. Despite these promising results, current systems remain highly dependent on operator skill, and cannot treat many tumors because there is little control of the size and shape of the zone of necrosis, and no control over ablator trajectory within tissue. Remedying this problem requires advances in end-effector design, precise steering of the ablator device to the desired target location, and real- time monitoring of the zone of necrosis to ensure complete treatment. Intra-procedure ultrasound imaging provides perhaps the optimal and most readily available method for targeting, but simultaneous manual handling of the B-mode ultrasound (US) probe and the ablator device is a challenging task that is prone to significant errors in the hands of even the most experienced physicians. Tissue deformation and target motion make it extremely difficult to place the ablator device precisely into the target. Irregularly shaped target volumes typically require multiple insertions and several overlapping thermal lesions, which are even more challenging to accomplish in a precise and timely manner without causing excessive damage to surrounding normal tissues. In answer to these problems, we propose to develop an innovative method for accurate tracking and tool registration with respect to spatially-registered intaoperative US volumes without relying on an external tracking device. This three-dimensional ultrasound (3DUS) will be integrated with a flexible, snake-like lightweight and inexpensive robotic, called the Active Cannula (AC), to facilitate precise placement of a steerable ultrasound thermal ablator into the liver and to monitor the progress of tissue ablation with real-time 3D registered ultrasound. Recent developments of implantable or interstitial high-power ultrasound applicators have demonstrated extremely controllable and penetrating heating patterns which can be shaped and dynamically altered, providing an ideal mechanism for conformable thermal surgery. This controllability and penetration is highly desirable and would provide significant improvement over existing RF and microwave (MW) technology used for minimally invasive thermal ablation of liver tumors. However, to date the extensive evaluation of this minimally invasive technology has been limited mostly to in vivo canine prostates and moderately perfused tissues, and have not included the design iterations and thorough evaluations necessary for treating tumors within highly perfused liver tissue. The preliminary thermal data from thermal therapy of perfused liver (Section C) are encouraging. Ultrasound Interstitial Thermal Therapy (USITT) technology is promising and we will extend the technology to optimize its use for the treatment of hepatic tumors. The overall goal of this research and development is to provide a true closed-loop system for steering, placement, guidance, percutaneous delivery of conformal ablative therapy, and on-line monitoring of treatment.